Antidepressants in elderly peopleBMJ 2011; 343 doi: http://dx.doi.org/10.1136/bmj.d4660 (Published 02 August 2011) Cite this as: BMJ 2011;343:d4660
- Ian B Hickie, professor
Because older people with clinical depression have high rates of concurrent medical illness, particularly cerebrovascular disease, they are at high risk of adverse events from most antidepressants.1 However, given the likelihood of poor functional outcomes and the increased risk of premature death by suicide, vascular disease, accident, or injury, safe and effective interventions are needed.1 2 3 In the linked cohort study (doi:10.1136/bmj.d4551), Coupland and colleagues assess the association between antidepressant treatment and risk of adverse outcomes in older people with depression in primary care.4
Before the 1990s, enthusiasm for drug treatment of depression was tempered by the risks associated with tricyclic antidepressants or monoamine oxidase inhibitors. With the arrival of selective serotonin reuptake inhibitors (SSRIs), which were reported to have far fewer major side effects treatment increased greatly, particularly in primary care settings.5 However, clinical trials had rarely focused on direct comparisons of benefits versus harms in older patients.
Although the relative benefits of new antidepressants are now clearer,6 there are still valid concerns about prescribing to younger7 and older patients. Although the reduction in suicide with the use of antidepressants is evident in older people,8 it has been harder to determine whether increased prescribing may also cause harm.
Coupland and colleagues assessed the effects of antidepressants in 60 706 patients aged 65 and over with a newly diagnosed episode of depression.4 Importantly, patients in this large primary care based cohort had the typical high rate of medical comorbidity. Although the authors highlight the limitations of their observational research, the study has clear implications for more informed prescribing and enhanced clinical monitoring.
All classes of antidepressant drugs were associated with increased risks of adverse events, and there were important differences in the type and frequency of serious effects across the various therapeutic classes. All of the SSRIs were associated with an increased risk of falls (hazard ratio 1.66, 95% confidence interval 1.58 to 1.73), and citalopram, escitalopram, and fluoxetine were also associated with hyponatraemia (1.52, 1.33 to 1.75). Trazodone, mirtazapine, and venlafaxine were associated with higher risks of all cause mortality and several potentially life threatening events, including attempted suicide or self harm and stroke or transient ischaemic attack.
The data show that the prescription of low dose tricyclic antidepressants remains popular—at least in the United Kingdom (31.6% of all antidepressant prescriptions). Unexpectedly, low dose tricyclic antidepressants did not have the highest hazard ratio for any of the adverse outcomes reported. However, for all the associations reported, important interactions between unknown patient factors and drug choice could still have occurred.
Certainly, venlafaxine is typically used in those with more severe or treatment resistant depression (which may be indicative of extensive medical comorbidity). Both trazodone and mirtazapine are more likely to be prescribed to patients with serious sleep disturbance or agitation, factors that again are often linked with more serious physical ill health. As the dose of tricyclic antidepressants increased, the risks of all cause mortality, falls, seizures, and fractures increased. For most adverse outcomes, the high risk periods were during the month after starting or stopping antidepressants.
The authors did not look at the extent to which antidepressant prescribing is used to treat other related symptoms such as headache, chronic pain, or sleep disturbance. Given the potential harms,9 10 the decision to prescribe for an older person with depression should not be taken lightly.
From a practice perspective, the high rate of prescribing described in the linked study (almost 90%) is noteworthy. Other data indicate that family practitioners prescribe psychoactive compounds to between one third and two thirds of people who present with psychological disorders.11 12 It is likely that doctors assign the diagnosis of clinical depression after they prescribe antidepressants (alone or in combination with psychological treatments). Although it seems that prescribing is reserved for more severe cases, or those who have failed to respond to psychological treatments, we need to be clearer that drugs should not be recommended as first line treatments for less severe depressive disorders, particularly in older patients.
The low rate of use of non-drug based treatments alone in this study has important implications for interpretation of these comparative analyses. These patients formed the “control” group but comprised only 10% of available subjects. A more clinically relevant approach may have been to use those people who received SSRIs as the control group (55% of the sample), because this group is most consistent with other standard clinical guidelines for persons with at least moderately severe depression.6 9 Future studies from this database, and other large health services resources, may be more clinically useful if they choose control groups that are representative of typical clinical practice. The database emphasises that for older people with at least moderately severe depression or other predictors of a likely response to drugs, the first line choice should remain those SSRIs that have the best ratio of benefits to harm (notably sertraline and citalopram).1 6 9 10 Although it is not necessary to seek a specialist opinion before starting treatment, clinicians, including those in primary care, need to be aware of the special circumstances surrounding the prescription of antidepressants to older people with depression (such as undetected cerebrovascular comorbidity, frequency and types of adverse events that can be life threatening).1 Older people therefore require careful monitoring for adverse effects, with provision of information (to the patient and carer) about the risks of falls, confusion, agitation, and increased suicidal ideation. They should also be advised that adverse effects are most commonly encountered during the first few weeks of treatment.1 4 For this reason, patients should be monitored at least weekly during the first month of treatment and again when drugs are stopped.4 Independently of the severity of depression or the prescription of drugs, all patients should be provided with appropriate psychological support and advice about behavioural interventions—particularly those aimed at increasing their daily activity and improving their sleeping patterns.1 9 10
Cite this as: BMJ 2011;343:d4660
Competing interests: The author has completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declares: no support from any organisation for the submitted work; IBH is supported principally by a National Health and Medical Research Council (NHMRC) Australian Medical Research Fellowship; research studies done by IBH are mainly funded by NHMRC project and programme grants; he has led or participated in other depression awareness projects for health professionals and the broader community, supported by governmental, community agency, and drug industry partners (Wyeth, Eli Lily, Servier, Pfizer, AstraZeneca); these programmes have focused on the identification and active management of depression and anxiety, with a strong emphasis on promotion of both non-pharmacological and pharmacological interventions; he has participated in a multicentre clinical trial of the effects of agomelatine on sleep architecture in depression; IBH was previously chief executive officer and then clinical adviser of beyondblue, the Australian government supported national depression initiative; he has participated in the development of guidelines for the treatment of depression, funded by the Australian government, and has served on advisory boards in relation to specific antidepressants, including nefazodone, duloxetine, and desvenlafaxine.
Provenance and peer review: Commissioned; not externally peer reviewed.